As part of a multinational cooperative research program sponsored by the World Health Organization, vascular manifestations of diabetes will be studied in a large population of Oklahoma Indians. Despite their great importance and their resistance to present therapeutic and preventive measures, both the microvascular and macrovascular lesions are still poorly understood. Recent evidence indicates, however, that there are major differences among populations in susceptibility to these lesions. Determination of the magnitude and character of these differences, and study of the genetic, racial, and environmental factors to which they relate, may be expected to yield useful information and clues applicable to their cause and mitigation. Previous comparative data have been difficult to interpret because methods have not been adequately standardized or detailed, and groups studied have very seldom been representative or large. Circumstances in Oklahoma are uniquely propitious because: 1. A large and virtually complete universe of Indian diabetics in a single circumscribe geographic area can be studied to determine and evaluate factors responsible for both intragroup and intergroup variations in susceptivility to these lesions (coronary, retinae, kidney, brain, and legs). 2. Because data will be collected using standardized methods, they can then be compared directly with data from several other populations (WHO study) in which racial, genetic, cultural, social, nutritional and environmental circumstances vary widely. 3. Some of our results and the characteristics of our sub-populations can also be related to previously published data in other groups including other Indian diabetic populations in which rates of certain vascular manifestations have been either high or low. 4. The design will also permit comparison and study of these lesions in several Oklahoma tribes and groups of tribes from widely divergent origins in-cluding two of the largest tribal groups in America (Plains Indians and Five Tribes Indians). Pilot studies have established the effectiveness of the local collaborative arrangements and the feasibility of the methods.